Targeting Metabolic Flexibility in ALS (MetFlex); Safety and Tolerability of Trimetazidine for the Treatment of ALS
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- The University of Queensland
- Enrollment
- 21
- Locations
- 3
- Primary Endpoint
- Incidence of Treatment-Emergent Adverse Events; Safety and Tolerability
Study Overview
Brief Summary
MetFlex is an investigator led, open-label, single-arm, Phase 2a trial to determine the safety and tolerability of trimetazidine for the treatment of amyotrophic lateral sclerosis/motor neuron disease (ALS/MND).
Detailed Description
The study will consist of a 4-week lead-in period to obtain a stable baseline measurement of clinical markers of disease and oxidative stress. After the lead-in phase, participants will receive trimetazidine for 12 weeks. Participants will visit the clinic at 6-week intervals, during which we will obtain a blood sample to measure the pharmacodynamic response. We will also collect information regarding the rate of disease progression (i.e. ALSFRS-R and SVC). At weeks 3 and 9 of treatment, participants will conduct a teleconference visit, during which we will collect data on ALSFRS-R. Adverse events will be collected and recorded throughout the entire trial duration. At the end of the on-treatment period, a close-out visit will occur after four weeks. The total study period per participant will be 20 weeks.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Age between 18 and 75 years
- •Signed informed consent prior to the initiation of any study-specific procedures
- •Familial or sporadic ALS/MND, defined as clinically possible, probable, or definite as per the El Escorial criteria
- •Relative TRICALS risk score between -6.0 to -2.0 (75% of patients with ALS/MND)
- •Metabolic index ≥110%, at the screening visit.
- •The use of riluzole will be permitted during the study. Individuals taking riluzole must be on a stable dose for at least 30 days prior to the baseline visit, or stopped taking riluzole at least 30 days prior to the baseline visit.
- •Ability to swallow tablets
- •Able to lie with torso elevated at a 35° angle for 30 minutes without respiratory support
- •Able to give informed consent (as judged by the investigator) and able to comply with all study visits and all study procedures
- •Females must not be able to become pregnant (e.g. post-menopausal, surgically sterile or using highly effective birth control methods) for the duration of the study. Highly effective methods of birth control are those with a failure rate of < 1% per year when employed consistently and correctly, e.g. Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
- •intravaginal
- •transdermal
- •Progestogen-only hormonal contraception associated with inhibition of ovulation:
- •injectable
- •implantable
- •intrauterine device (IUD)
- •intrauterine hormone-releasing system ( IUS)
- •vasectomised partner
- •Females of child-bearing potential must have a negative serum pregnancy test at screening and baseline and be non-lactating
Exclusion Criteria
- •Unable to provide informed consent
- •History of, or current diagnosis of diabetes or medical condition that impacts whole body energy expenditure (e.g. Hashimoto's, heart disease)
- •Parkinson's disease or parkinsonism, tremor, restless-leg syndrome
- •Safety Laboratory Criteria at screening related to significant kidney disease:
- •Creatinine clearance < 50 mL / min (Cockcroft-Gault) based on Cystatin C
- •Tracheostomy or non-invasive ventilation (NIV) use > 22 hours per day
- •Inability to swallow tablets
- •Contraindication therapy:
- •Allergy for one of the product's active pharmaceutical ingredients (APIs) or excipients.
- •Antihypertensive treatment [Trimetazidine may cause hypotension]
- •Evidence of malignant disease
- •Significant neuromuscular disease other than ALS/MND
- •Ongoing disease that may cause neuropathy
- •Pregnancy or breastfeeding
- •Females actively seeking to become pregnant who are not using an adequate form of contraceptive as detailed in the Inclusion criteria.
- •Deprivation of freedom by administrative or court order
Arms & Interventions
Experimental
Trimetazidine 35mg
Intervention: Trimetazidine Dihydrochloride (Drug)
Outcomes
Primary Outcomes
Incidence of Treatment-Emergent Adverse Events; Safety and Tolerability
Time Frame: 16 weeks
The occurrence of adverse events, as assessed by Common Terminology Criteria for AEs Version 5, during the 12-week on-treatment period and 4-week wash-out period (16 weeks total).
Level of expression of oxidative stress markers in the plasma and/or serum of trial participants
Time Frame: 16 weeks
Expression of oxidative stress markers (malondialdehyde, 8-hydroxy-2'-deoxyguanosine, interleukin-6; assessed by liquid chromatography-mass spectrometry/mass-spectrometry or multiplexing) in the plasma and/or serum of trial participants throughout the treatment period (12-week) and at the end of the wash-out period (4 weeks)
Secondary Outcomes
- Level of expression of oxidative stress markers in the plasma and/or serum of trial participants to inform future clinical trials in ALS/MND(16 weeks)